Imidazole → 7-Bromo-4-((tert-butyldiphenylsilyl)oxy)-1,2,3,4-tetrahydro-1,8-naphthyridine

HRID 1777930Notes

Reaction equation

[Br:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]([OH:12])[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1.N1C=CN=C1.[C:18]([Si:22](Cl)([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([CH3:21])([CH3:20])[CH3:19]>CN(C=O)C>[Br:1][C:2]1[N:11]=[C:10]2[C:5]([CH:6]([O:12][Si:22]([C:18]([CH3:21])([CH3:20])[CH3:19])([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:7][CH2:8][NH:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of 7-bromo-1,2,3,4-tetrahydro-1,8-naphthyridin-4-ol (intermediate 73, 420 mg, 1.83 mmol) in DMF (5 ml) and treated with imidazole (374 mg, 5.50 mmol) and tert-butylchlorodiphenylsilane (0.565 ml, 2.20 mmol) and stirred at 25° C. for 16 h. The reaction mixture was quenched with water and extracted with EtOAc (3×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 30:70) and reverse phase chromatography (43 g C18 cartridge, 0.1% TFA in water/acetonitrile 90:10 to 0:100) to give the title compound as a white solid. (UPLC-MS 3) tR 1.61; ESI-MS 467.2, 469.2 [M+H]+.

Workup

customThe reaction mixture was quenched with water
extractionextracted with EtOAc (3×)
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 30:70)

Sources & evidence

ORD record: ord-54804b69df4842bcb3cffe8d6d5823a1
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09266883B2

Reaction notes

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